The interaction of the tumor cell with its extracellular matrix may play an important role in determining its metastatic and invasive properties. We have identified, isolated, characterized, and cloned three laminin binding proteins that are present in both normal and neoplastic tissues. All three proteins share a common epitope, and specifically bind to the poly-N-acetyllactosamine chains of laminin. The 67 kDa high affinity laminin receptor (67LR) has been previously characterized as a nonintegrin binding protein and has been molecularly cloned. It is expressed to a greater degree in metastatic tissues than in benign conditions in a variety of tissue-specific neoplasms. The 67LR is synthesized from a cytoplasmic precursor with an approximate molecular mass of 37 kDa. Using synthetic peptides, we have identified a 20 amino acid region of the precursor, designated peptide G, that binds directly to laminin with high affinity and that can inhibit attachment of laminin-coated melanoma cells to endothelium. We recently showed that this peptide enhances the metastatic potential of cancer cells via hematogenous routes. We have also identified a specific site on the laminin molecule to which the 67LR binds. We recently purified two other nonintegrin laminin binding proteins, HLBP31 and HLBP14, from human cancer cell lines. HLBP31 and HLBP14 have apparent molecular masses of 31 kDa and 14 kDa, respectively. We have used cDNA clones of the 67LR and the HLBP31 to assess the relative expression of mRNA in human colorectal carcinomas. The level of HLBP31 mRNA is inversely modulated with the 67LR in human colorectal carcinomas. Using the in situ hybridization technique, we established that the colonic cancer cells express more 67LR mRNA than do benign epithelial mucosal cells. Future studies will determine if the selective use of different laminin binding proteins by colonic cancer cells may play a functional role in the disease process.